The objective of this research application is to utilize BIOTEK's transdermal drug delivery system for the development of a sustained transdermal delivery system for estradiol and levonorgestrel for use in estrogen replacement therapy. Conditions for estradiol and levonorgestrel transdermal delivery were previously developed for a contraceptive patch which successfully concluded clinical trials. Phase I support is sought to demonstrate the feasibility of this approach for the development of a 48 hour estrogen replacement patch in vitro and in vivo. During Phase II the variables which affect rate and duration of delivery will be finalized. Toxicology studies and the necessary documentation of manufacturing specifications will be completed so that an Investigative New Drug (IND) application can be approved and clinical tests conducted. The results of the Phase II studies will be the basis for industrial support for the commercialization of the product.